Matrix metalloproteinases (MMPs) are a protein family of zinc-containing endopeptidases. Especially, MMPs are essential in (neuro)inflammation. MMPs act as enzymes capable of catalyzing the hydrolysis of collagen. MMP-3 binds to type I collagen but does not cleave the native triple-helix. MMP-2 cleaves types I, II, and III collagen. MMP-13 cleaves the N-terminal telopeptide region of the resistant type I collagen. In particular, PD-166793 is an MMP catalytic site inhibitor.

The MMPs are a family of Zn²⁺-dependent endopeptidases. Additionally, MMPs play an active role in immune processes by cleaving various molecules, including growth factors, death receptors, chemokines, and cytokines. MMPs are extracellular proteolytic enzymes involved in the degradation of both matrix and nonmatrix proteins. PD-166793 is a wide‐broad spectrum MMP inhibitor. Moreover, PD-166793 completely prevents angiotensin-II/tachypacing-induced diastolic dysfunction in vivo.

PD-166793 acts as a potent inhibitor against MMP−2, MMP−3, and MMP−13 (IC₅₀= 47, 12, and 8 nM, respectively) and a weaker inhibitor of MMP−1, MMP−7, MMP−9, and MMP−14 (IC₅₀= 6.1, 7.2, 7.9, and 0.24 μM, respectively). PD-166793 inhibits MMP-2 in a concentration-dependent manner in left ventricular myocardial extracts (50% inhibition by 5 μM PD166793). In addition, the MMPs inhibitor PD-166793 (2 μM) attenuated the ONOO⁻-the induced decline of cardiac mechanical function. Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Furthermore, PD-166793 decreases the in vitro invasive cell behavior of ENU1546. ENU1564 is a Carcinogen-induced mammary adenocarcinoma cell line. Besides, MMPs play a key role in a post-MI left ventricular rupture in animal models.

Together, PD-166793 acts as a general inhibitor of MMP activity. MMP-2, MMP-3, and MMP-9 may be involved in the process of metastasis of breast cancer to the brain.

Reference:
Nina Kaludercic, et al. Inhibiting metalloproteases with PD 166793 in heart failure: impact on cardiac remodeling and beyond. Cardiovasc Ther. Spring 2008;26(1):24-37.